Autologous T-Cells Expressing a Second Generation CAR for Treatment of T-Cell Malignancies Expressing CD5 Antigen

Launched by BAYLOR COLLEGE OF MEDICINE · Mar 10, 2017

Keywords

ClinConnect Summary

This clinical trial is studying a new treatment for patients with certain types of blood cancers, specifically T-cell leukemia and lymphoma. The treatment involves using a special type of immune cell called T cells, which are designed to recognize and attack cancer cells. In this study, researchers will take T cells from either the patient or a previous donor, modify them in the lab to enhance their cancer-fighting abilities, and then give them back to the patient. The goal is to see how well these modified T cells can survive in the body and fight the cancer.

To participate in this trial, patients must be diagnosed with specific types of T-cell leukemia or lymphoma, be under 75 years old, and have a life expectancy of at least 12 weeks. They should also have a suitable donor if their own T cells cannot be used. Participants can expect close monitoring throughout the study to assess the effectiveness and safety of the treatment. It's important to note that this is an experimental approach, meaning it has not yet been approved by the FDA, but it offers hope for patients whose current treatment options may be limited.

Gender

ALL

Eligibility criteria

• • Procurement Inclusion Criteria for the Patient
• Referred patients (Group A) or their previous HSCT donors (Group B) will initially be consented for procurement of blood for generation of the transduced ATL. Patient eligibility criteria at this stage include:
• • 1. Diagnosis of recurrent T-cell acute lymphoblastic leukemia (T-ALL), T-cell acute lymphoblastic lymphoma (T-LLy), or T-non-Hodgkin lymphoma (T-NHL, including Angioimmunoblastic T-cell lymphoma (AITL), Enteropathy-associated T-cell lymphoma (EATL), Monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL), Peripheral T-cell lymphoma (PTCL) NOS, Anaplastic large cell lymphoma (ALCL), Adult T-cell leukemia/lymphoma, T cell prolymphocytic leukemia with symptomatic disease, Extranodal NK/T cell lymphoma, Mycosis fungoides/ Sezary Syndrome Stage IIB or higher))
• • AND
• • Group A (auto arm): Transplant naïve or relapsed post-allogeneic HSCT OR
• • Group B (allo arm): Relapsed post-allogeneic HSCT with previous HSCT donor from whom allogeneic MAGENTA CAR T cells can be manufactured
• • AND
• • Suitable for allogeneic hematopoietic stem cell transplant (HSCT) with confirmation of an identified eligible allo-HSCT donor by FACT accredited institution
• • Confirmation that the center plans to proceed with transplant if CD5.CAR treatment induces a complete remission.
• • For T-NHL subjects, eligibility will be confined to disease stages where allogeneic HSCT is indicated.
• • 2. CD5-positive tumor (result can be pending at this time). \> 50% CD5 + blasts by flow cytometry or immunohistochemistry (tissue) assessed by a CLIA certified Flow Cytometry/Pathology laboratory.
• • 3. Age ≤75 years old. NOTE: The first six (6) patients treated on the study should be adults (\>18 yrs of age).
• • 4. Life expectancy of greater than 12 weeks.
• • 5. Patients must have an available partially-HLA matched allogeneic EBV-specific T cell line on a BCM IRB approved protocol which can be used as treatment in the event of uncontrolled EBV reactivation
• • 6. Informed consent explained to, understood by and signed by patient/guardian. Patient/guardian given copy of informed consent.
• • 7. Hgb greather than or equal to 7.0 g/dL (can be transfused)
• 8. If pheresis required to collect blood:
• • Creatinine \<1.5 × upper limit normal
• • AST \<1.5 × upper limit normal
• • PT and APTT \<1.5 × upper limit normal
• • Procurement Exclusion Criteria for the Patient (Group A)
• • 1. Active infection requiring antibiotics.
• • 2. Active infection with HIV
• • 3. History of other cancer (except non-melanoma skin cancer or in situ breast cancer or cervix cancer) unless the tumor was successfully treated with curative intent at least 2 years before trial entry.
• Procurement Inclusion Criteria for Normal Healthy Donor (Group B):
• • 1. Donor must be prior hematopoietic stem cell transplant donor for patients relapsed post-allogeneic HSCT. Prior transplant donors will be screened with the standard blood bank donor questionnaire, medical history, and testing for infectious disease markers (IDMs; which may be pending at the time of blood collection). Medical history may be obtained by the patient's primary/referring transplant team if collection is being done remotely. The physician assessment, donor questionnaire, and IDMs will be reviewed by the principle investigator or appropriate designee to confirm/provide final eligibility determination and documented in the donor's medical record.
• • 2. Informed consent explained to, understood by and signed by donor/LAR. Donor/LAR given copy of informed consent.
• • Treatment Inclusion Criteria
• Patients must meet the following eligibility criteria to be included for treatment:
• • 1. Diagnosis of recurrent T-cell acute lymphoblastic leukemia (T-ALL), T-cell acute lymphoblastic lymphoma (T-LLy), or T-non-Hodgkin lymphoma (T-NHL, including Angioimmunoblastic T-cell lymphoma (AITL), Enteropathy-associated T-cell lymphoma (EATL), Monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL), Peripheral T-cell lymphoma (PTCL) NOS, Anaplastic large cell lymphoma (ALCL), Adult T-cell leukemia/lymphoma, T cell prolymphocytic leukemia with symptomatic disease, Extranodal NK/T cell lymphoma, Mycosis fungoides/ Sezary Syndrome Stage IIB or higher))
• • AND
• • Group A (auto arm): Transplant naïve or relapsed post-allogeneic HSCT OR
• • Group B (allo arm): Relapsed post-allogeneic HSCT with previous HSCT donor from whom allogeneic MAGENTA CAR T cells can be manufactured
• • AND
• • Suitable for allogeneic hematopoietic stem cell transplant (HSCT) with confirmation of an identified eligible allo-HSCT donor by FACT accredited institution
• • Confirmation that the center plans to proceed with transplant if CD5.CAR treatment induces a complete remission.
• • For T-NHL subjects, eligibility will be confined to disease stages where allogeneic HSCT is indicated.
• • 2. CD5-positive tumor. \>50% CD5 + blasts by flow cytometry or immunohistochemistry (tissue) assessed by a CLIA certified Flow Cytometry/Pathology laboratory.
• • 3. Age \<75 years old. NOTE: The first six (6) patients treated on the study should be adults (\>18 yrs of age).
• • 4. Bilirubin less than 3 times the upper limit of normal.
• • 5. AST less than 5 times the upper limit of normal.
• • 6. Estimated GFR \> 60 mL/min.
• • 7. Pulse oximetry of \> 90% on room air.
• • 8. Karnofsky or Lansky score of ≥ 60%.
• • 9. Recovered from acute toxic effects of prior chemotherapy at least one week before entering this study.
• • 10. ≥ 60 days post-allogeneic HSCT at time of treatment.
• • 11. Patients must have an available partially-HLA matched allogeneic EBV-specific T cell line on a BCM IRB approved protocol which can be used as treatment in the event of uncontrolled EBV reactivation.
• • 12. Sexually active patients must be willing to utilize one of the more effective birth control methods during the study and for 6 months after the study is concluded. The male partner should use a condom.
• • 13. Informed consent explained to, understood by, and signed by patient/guardian. Patient/guardian given copy of informed consent.
• • Treatment Exclusion Criteria
• • 1. Currently receiving any investigational agents or having received any tumor vaccines within the previous 6 weeks.
• • 2. History of hypersensitivity reactions to murine protein-containing products.
• • 3. Pregnant or lactating.
• • 4. Tumor in a location where enlargement could cause airway obstruction.
• • 5. Active infection with HIV.
• • 6. Clinically significant viral infection or uncontrolled viral reactivation of EBV, CMV, Adv, BK-virus, or HHV-6.
• • 7. Evidence of acute GVHD \> Grade II or active chronic GVHD \> mild global severity score
• • 8. Currently taking corticosteroids for therapy of GVHD at a dose of \>0.5mg/kg prednisone equivalent
• • 9. Patients who have received Immunosuppressive Treatment (IST) for GVHD within 28 days of infusion
• • 10. Patients who have received donor lymphocyte infusion (DLI) within 28 days of infusion
• • 11. Any of the following cardiac criteria: Atrial fibrillation/flutter; Myocardial infarction within the last 12 months; Prolonged QT syndrome or secondary prolonged QT, per investigator discretion. Cardiac echocardiography with LVSF\<30% or LVEF\<50%; or clinically significant pericardial effusion. Cardiac dysfunction NYHA III or IV (Confirmation of absence of these conditions within 12 months of treatment)
• • 12. CNS abnormalities: Presence of CNS-3 disease defined as detectable cerebrospinal blast cells in a sample of CSF with ≥ 5 WBCs per mm3; History or presence of any CNS disorder such as a uncontrolled seizure disorder, cerebrovascular ischemia/hemorrhage within prior 6 months, dementia, cerebellar disease, or any autoimmune disease with CNS involvement.